P371: PONATINIB AS A PROPHYLACTIC OR PRE-EMPTIVE STRATEGY TO PREVENT CYTOLOGICAL RELAPSE AFTER ALLO-SCT IN PATIENTS WITH PH POS ALL TRANSPLANTED IN COMPLETE CYTOLOGICAL REMISSION
Authors: Anna Candoni, Patrizia Chiusolo, Davide Lazzarotto, Cristina Papayannidis, Cristina Skert, Fabio Giglio, Nicola Stefano Fracchiolla, Michelina Dargenio, Sabina Chiaretti, Silvia Trappolini, Chiara Sartor, Paola Bresciani, Angela Cuoghi, Attilio Olivieri, Renato Fanin
Journal: HemaSphere (2023)

Background: The proper administration of TKIs after Allo-SCT in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) remains controversial and the TKI approach (prophylactic, pre-emptive or salvage) is still heterogeneous through transplant centers. In this context, very little is known about the efficacy and safety of third-generation TKIs Aims: Here we present the preliminary results of the ongoing multicentre study to analyse efficacy and safety profile of therapy with ponatinib (PONA) after Allo-SCT to prevent Ph+ ALL cytological relapse. Methods: We report the analysis of the first 48 included patients (pts) with Ph+ ALL (median age 49 years; range 20-70) who received PONA after their Allo-SCT (donors: 24 MUD, 11 siblings HLA Id and 9 Haplo and 4CB). All 48 pts received Allo-SCT while in complete cytological remission (cCR) and 26 pts (54%) had positive minimal residual disease (MRD+) before Allo-SCT. PONA was administered after Allo-SCT prophylactically (starting with MRD neg) in 26 pts or pre-emptively (starting with MRD positivity post-SCT and without hematological relapse) in 22 pts Results: The 26 pts treated prophylactically with PONA started treatment earlier, at a median of 4,3 months (range 1,5-6) after Allo-SCT, than the 22 pts treated pre-emptively, who started PONA at a median of 7,4 months (range 2-63) after Allo-SCT (p=0,01). The median starting dose of PONA was 30 mg/day (range 15-45). Reduction of the initial dose was required in 15/48 (31%) of cases (mainly in those receiving an initial dose of 45 mg/day), but a permanent discontinuation of PONA, due to toxicity, was required in only 5/48 pts (10,4%). No deaths due to PONA-related adverse events were reported. The mean and median follow-up time after Allo-SCT was 40±26 and 34 months (range 7,7-118), respectively. At last follow-up, the median duration of PONA therapy was 22 months (range 2-100). Detailed data on the safety profile of PONA were collected. In addition to PONA, 10 pts received donor lymphocyte infusions. The 5-year OS and RFS after Allo-SCT of all 48 pts were 92% and 71%, respectively (Figure 1a and 1b). The 5-year RFS after Allo-SCT of pts who received PONA as prophylaxis was 95% and it was 57% for those who received PONA pre-emptively (log-rank p=0,02). Summary/Conclusion: Preliminary data obtained from this analysis, in a homogeneous population of Ph+ ALL undergoing Allo-SCT while in CcR, although with the caution of the retrospective data, support the efficacy and safety of PONA as a maintenance strategy after Allo-SCT, resulting in a high probability of OS and DFS and in a low rate of discontinuation due to PONA-related toxicity. However, in the majority of cases where a daily dose of 45 mg was started a dose reduction to 30-15 mg/day was required, which seems to be the appropriate dose to balance efficacy and tolerability.Keywords: allo BMT, Ph+ ALL, Acute lymphoblastic leukemia